F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability
Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To cl...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-07-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2017.1303022 |
| _version_ | 1797677633116307456 |
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| author | Jingjing Kang Jie Gao Wenwu Yao Lin Kang Shan Gao Hao Yang Bin Ji Ping Li Jing Liu Jiahao Yao Wenwen Xin Baohua Zhao Jinglin Wang |
| author_facet | Jingjing Kang Jie Gao Wenwu Yao Lin Kang Shan Gao Hao Yang Bin Ji Ping Li Jing Liu Jiahao Yao Wenwen Xin Baohua Zhao Jinglin Wang |
| author_sort | Jingjing Kang |
| collection | DOAJ |
| description | Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+ release from intracellular Ca2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins. |
| first_indexed | 2024-03-11T22:47:09Z |
| format | Article |
| id | doaj.art-aff8dd9d97af4f9fb46f14b280df3248 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:47:09Z |
| publishDate | 2017-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-aff8dd9d97af4f9fb46f14b280df32482023-09-22T08:17:49ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2017-07-011371598160810.1080/21645515.2017.13030221303022F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capabilityJingjing Kang0Jie Gao1Wenwu Yao2Lin Kang3Shan Gao4Hao Yang5Bin Ji6Ping Li7Jing Liu8Jiahao Yao9Wenwen Xin10Baohua Zhao11Jinglin Wang12Life Science Institute of Hebei Normal UniversityLife Science Institute of Hebei Normal UniversityInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyInstitute of Microbiology and EpidemiologyLife Science Institute of Hebei Normal UniversityInstitute of Microbiology and EpidemiologyEpsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+ release from intracellular Ca2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins.http://dx.doi.org/10.1080/21645515.2017.1303022clostridium perfringensepsilon toxin (etx)mutantmechanismcell-bindingpore-forming |
| spellingShingle | Jingjing Kang Jie Gao Wenwu Yao Lin Kang Shan Gao Hao Yang Bin Ji Ping Li Jing Liu Jiahao Yao Wenwen Xin Baohua Zhao Jinglin Wang F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability Human Vaccines & Immunotherapeutics clostridium perfringens epsilon toxin (etx) mutant mechanism cell-binding pore-forming |
| title | F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability |
| title_full | F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability |
| title_fullStr | F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability |
| title_full_unstemmed | F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability |
| title_short | F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability |
| title_sort | f199e substitution reduced toxicity of clostridium perfringens epsilon toxin by depriving the receptor binding capability |
| topic | clostridium perfringens epsilon toxin (etx) mutant mechanism cell-binding pore-forming |
| url | http://dx.doi.org/10.1080/21645515.2017.1303022 |
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